Variant X-70277474-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004312.3(ARR3):c.554G>C(p.Arg185Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ARR3
NM_004312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.934

Variant links:

Genes affected

ARR3 (HGNC:710): (arrestin 3) The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]

ARR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3 link	c.554G>C	p.Arg185Pro	missense_variant	Exon 9 of 17	ENST00000307959.9	NP_004303.2	P36575-1
ARR3	XM_047442105.1 link	c.578G>C	p.Arg193Pro	missense_variant	Exon 8 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9 link	c.554G>C	p.Arg185Pro	missense_variant	Exon 9 of 17	1	NM_004312.3	ENSP00000311538.8		P36575-1
ARR3	ENST00000374495.7 link	c.554G>C	p.Arg185Pro	missense_variant	Exon 9 of 16	1		ENSP00000363619.3		P36575-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097627

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362999

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.554G>C (p.R185P) alteration is located in exon 9 (coding exon 8) of the ARR3 gene. This alteration results from a G to C substitution at nucleotide position 554, causing the arginine (R) at amino acid position 185 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

.;.;D

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.0062

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.3

D;.;D

REVEL

Benign

0.18

Sift

Uncertain

0.012

D;.;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.97

D;.;D

Vest4

0.74

MutPred

0.52

Loss of MoRF binding (P = 0.0471);Loss of MoRF binding (P = 0.0471);Loss of MoRF binding (P = 0.0471);

MVP

0.33

MPC

0.28

ClinPred

0.93

GERP RS

3.7

Varity_R

0.85

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over